2. Classification
• Acquired:
(autoimmune, infectious,toxiderma )
• Hereditary:
(Epidermolysis Bullosa, ichtyosis bullosa )
Fine JD, Management of acquired bullous skin diseases; New England Journal of
Medecine.
Bickle K, Roark T; Autoimmune Bullous dermatoses: A Review; American family
physician.
6. Epidermal and Epidermal-Dermal
Cohesion
• Desmosomes, hemidesmosomes, and the epidermal
basement membrane
• They represent distinct molecular adhesion complexes
• Mutations in the genes encoding protein components of
the above cause hereditary skin diseases
• These proteins are targeted in autoimmune skin
blistering diseases ( pemphigus or pemphigoid group
and in epidermolysis bullosa acquisita)
7. Epidermal and Epidermal-Dermal
Cohesion
• The major components of desmosomes belong to three
major gene families:
Plakins (desmoplakins) , Armadillo proteins (plakophilins and
plakoglobins), and Desmosomal cadherins (desmogleins,
desmocollins).
Cytoplasmic proteins (desmoplakins , plakophilins and
plakoglobins) and
Transmenbrane proteins (desmogleins and desmocollins)
8.
9. Epidermal and Epidermal-
Dermal Cohesion
• The hemidesmosomal components comprise:
1. Cytoplasmic proteins [ plakin homologues (plectine,
BPAG1)]
2. Trasmembrane components [integrins, and collagenous
transmembrane (BPAG2)].
• All basement membranes contain collagen IV, laminins,
nidogens, and perlecan.
• Anchoring fibrils ( to the dermis) are composed mainly of
collagen VII
25. Paraneoplastic Pemphigus
• Most common malignancy associated is
non-Hodgkin lymphoma
• Next most common in frequency are
chronic lymphocytic leukemia,
Castleman’s disease, and thymoma.
• Also: Waldenstrom’s macroglobulinemia,
sarcomas
28. Paraneoplastic Pemphigus
-
Histology
• Suprabasilar acantholysis and basal cell
vacuolation + lymphocytic exocytosis and
dyskeratotic keratinocytes
• IgG + C3 deposits within the intercellular
spaces and along the basement membrane
• Desmoplakin I and II
29.
30. Paraneoplastic Pemphigus
Evolution and treatment
May precede clinical appearance of neoplasm
• Very poor prognosis
• Treatment usually unsuccessful
• Remission if a benign tumor is resected
• Immunosuppressive treatment, plasmapheresis,
immunophoresis.
32. Bullous Pemphigoid
• Mainly in the elderly, rarely in children
• Involvement of mucous membranes <<< PV
• May start as urticarial eruption, pruritus+++
• Blisters are tense, less easily ruptured
• Topography: medial thighs, axillae, groin, abdomen,
flexor forearms, lower legs, oral cavity, anus, genital
mucosa.
• No scar formation following the lesions of PB.
34. Bullous Pemphigoid
• Subepidermal blister, dermal inflammation ( L, H, Eo)
• EM: Lamina lucida of BM ( loss of anchoring filaments
and hemidesmosomes)
• DIF: deposition of IgG and C3 along the basement
membrane in a linear pattern
• IIF: IgG antibodies against basement membrane zone
• Target antigen: Pemphigoid antigen 1 (230 KD ) and 2 (
180 KD) localised in hemidesmosomes
40. Herpes gestationis
or
Pemphigoid Gestationis
• Bullous pemphigoid of pregnancy
• Develop during the second and third trimesters
• Abrupt onset of extremely pruritic urticarial
papules and blisters (abdomen,trunk)
• Resolves spontaneously within weeks to months
after delivery
• Dramatic flares can occur at or immediately after
delivery
• May recur with subsequent pregnancies
41.
42.
43.
44. Herpes Gestationis
• No increase in fetal or maternal mortality
• Greater prevalence of premature and
small-for-gestational-age (SGA) babies
• 5-10% of infants born to affected mothers
may present with transient cutaneous
involvement that resolves as maternal
autoantibodies are cleared.
45. Treatment
• Prednisone at 0.5 mg/kg/d (starting dose)
• Tapered to minimum dose required to
control the disease
• Steroid-sparing agents may be used after
delivery in resistant cases
• Topical steroids may be initiated in mild
cases
47. Cicatricial Pemphigoid
• Severe erosive lesions of the skin and mucous
membrane
• Skin involvement in 1/3 of patients
• Tense bullae, erosions, ulcers
• Healing with scars
• Ocular lesions scarring, fibrosis, blindness
• Esophagus occlusion, supraglottic stenosis
48.
49. Cicatricial Pemphigoid
• Subepidermal blisters + mixed inflammatory infiltrate
• Fibroblast proliferation in older lesions
• DIF: linear deposition of C3 and IgG along the
basement membrane ( IgA and IgM )
• EM: loss of anchoring filaments
• Target Antigens: BPA2 (180 KD), laminin-5 Ag
50.
51. Course and Treatment
• Chronic progressive disease
• Multidisciplinary approach
(otolaryngology, ophtalmology, gastroenterology,
gynecology)
• Topical corticosteroids ( mouthwash)
• Dapsone ( 50 to 100 mg/day) +/- systemic steroids
• Ocular involvement: systemic steroids +
cyclophosphamide ( 0.5 to 2 mg/kg/j) or azathioprine or
mycophenolate mofetil ( 1.5 to 3 g/day)
•
53. Dermatitis herpetiformis
• Onset: 20 and 40 years
• Papulovesicular and urticarial lesions (wheals)
• Extensor surfaces in a symmetric distribution
• Pruritus+++
• Associated with a gluten-sensitive enteropathy
56. Dermatitis herpetiformis
• Subepidermal vesicles, neutrophilic
microabcesses in dermal papillae and
dermal infiltration of N + Eo
• DIF: IgA in tips of dermal papillae
• Positive Antiendomysial, antigliadine,
antitransglutaminase antibodies in sera
61. Linear IgA dermatosis
• Children and young adults
• Pruritic annular papules, vesicules
(« collarettes »)
• Extensor surfaces, symmetric distribution
• Possible mucous involvement
68. Patient with epidermolysis bullosa acquisita who has
severe blistering, erosions, scarring, and milia
formation on trauma-prone areas of her skin. This is
the classic presentation
69. Histopathology
• Subepidermal (below lamina densa)
• DIF: IgG and/or C3 linearly along the
dermoepidermal junction
• A positive DIF and IgG deposits within the sub-
lamina densa zone are necessary criteria for
the diagnosis of EBA.
• Target antigen : type VII collagen (290 and 145
kd)
70.
71.
72. Epidermolysis bullosa acquisita
• Related features may include an
underlying systemic disease such as
inflammatory bowel disease.
• Treatment options limited and often
difficult
73. Classification
• Acquired:
(autoimmune, infectious, toxiderma )
• Hereditary:
(Epidermolysis Bullosa, ichtyosis bullosa )
Fine JD, Management of acquired bullous skin diseases; New England Journal of
Medecine.
Bickle K, Roark T; Autoimmune Bullous dermatoses: A Review; American family
physician.
75. Erythema Multiforme
• Cell-mediated hypersensitivity reaction
• Minor form
• Causes:
- infectious ( Herpes simplex,
Mycoplasma Pneumoniae, Chlamydiae)
- drugs
• 20% occur in childhood
76. Erythema Multiforme
• Lesions are red papules that
evolve into target lesions
• Blister or crust in the central
zone
• Topography: face and acral
• Mucous membrane
involvement: light to severe
77. Treatment
• Oral corticosteroids?, thalidomide, dapsone,
other immunosuppressive agents
• Acyclovir, Valacyclovir ( therapeutic trial even if
no preceding herpes simplex infection has been
documented)
• Oral erythromycine (chlamidiae, mycoplasma)
• Ophtalmologic care (artificial tears, topical
vitamin A)
78. Clinical criteria for Stevens-
Johnson syndrome
• Acute mucocutaneous syndrome
• Prodrome of upper respiratory illness with fever, cough, headache
and malaise
• Abrupt onset of symmetrical red papules
• Rapid evolution to target lesions, large bullae or extensive areas of
denuded skin.
• At least two mucosal surfaces involved with erosions and
crusting
• Duration of at least 3 weeks
82. Eetiology and pathogenesis
• Preceding infections with Mycoplasma
pneumoniae
• Drugs: NSAIDs, anticonvulsivants,
penicillins, tetracycline, doxycycline,
sulphonaides
• Combination of infection and drug
84. Prognosis and treatment
• 4 to 6 weeks course
• Complications: dehydration, electrolyte
imbalance, secondary bacterial infection,
cutaneous scarring and dyspigmentation.
• Ocular sequalae, contracture over joints
85. Prognosis and treatment
• Hospitalization
• Immediate withdrawal of any suspected
drug
• Correction of fluid and electrolyte
imbalance
• Warming the environment
• Prevention of secondary infection and
sepsis
86. Treatment
• Use of corticosteroids is controversial
• May lower the period of acute eruption and
fever
• May adversely affect morbidity and mortality
• Other: Mycophenolate Mofetil, IVIG
87. Toxic Epidermal Necrolysis
• Severe, life-threatening, bullous disease
• Widespread detachment of the epidermis denudation
of large areas of body surface > 30%
• Mucous membrane +++
• Cause: systemically administered medication
• Differential diagnosis: staphylococcal scalded skin
syndrome
90. Treatment
• Use of corticosteroids is controversial and
cannot be recommended
• IVIG may be of benefit (risk for
anaphylaxis)
• Supportive treatment +++ (meticulous
nursing care in burn units, large volumes
of fluids, electrolytes etc…)
91. Classification
• Acquired:
(autoimmune, infectious, toxiderma )
• Hereditary:
(Epidermolysis Bullosa, ichtyosis bullosa )
Fine JD, Management of acquired bullous skin diseases; New England Journal of Medecine.
Bickle K, Roark T; Autoimmune Bullous dermatoses: A Review; American family physician.
102. Epidermolysis Bullosa
Simplex
• Blisters on hands and feet +++, trunk and limbs
• Plamo-plantar hyperkeratosis
• Nail dystrophy
• Oropharyngeal blistering ( D-M EBS)
• Hot environment,friction and trauma may induce
blistering
109. Dystrophic Epidermolysis
Bullosa
• Tendency for blistered area to heal with atrophic
scarring
• Milia in recently healed areas
• Development of joint contractures and fusion of
fingers and toes
• Tendency for epitheliomas in reccurently
ulcerated and scarred areas
110.
111. Dystrophic Epidermolysis
Bullosa
• Blistering of the oral, pharyngeal and oesophageal mucosa
Leading to:
- Reduced nutritional intake
- Progressive contraction of the mouth
- Progressive fixation of the tongue
- Oesophageal stricture
• Conjunctival bullae
• Genitourinary tract strictures
112. Prognosis in DEB
• Extraordinary variation in prognosis
• Correlates with the amount of collagen VII
at the basement membrane
• Complete absence suggests a worse
outlook
113. Junctional epidermolysis bullosa
• Herlitz JEB laminine 5
• non-Herlitz JEBcollagen XVII laminine 5
• JEB with pyloric atresia integrin alpha6 B4
120. Treatment of EB
• General skin care ( special non-adhesive
dressings and bandages)
• Pain control ++++
• Management of complications
• Conservative approach ++++
121. Classification
• Acquired:
(autoimmune, infectious, toxiderma )
• Hereditary:
(Epidermolysis Bullosa, ichtyosis bullosa )
Fine JD, Management of acquired bullous skin diseases; New England Journal of Medecine.
Bickle K, Roark T; Autoimmune Bullous dermatoses: A Review; American family physician.
122. Ichtyosis bullosa
• Genetic skin disease ( genes encoding keratin)
• Widespread blistering in infancy
• Blistering improves with age
• Hyperkeratosis, desquamation, erythroderma,
lichenification…
